PMID- 31163672 OWN - NLM STAT- MEDLINE DCOM- 20200106 LR - 20200225 IS - 1420-3049 (Electronic) IS - 1420-3049 (Linking) VI - 24 IP - 11 DP - 2019 Jun 3 TI - Novel Targeted Nano-Parthenolide Molecule against NF-kB in Acute Myeloid Leukemia. LID - 10.3390/molecules24112103 [doi] LID - 2103 AB - The targeted nano-encapsulation of anticancer drugs can improve drug delivery and the selective targeting of cancer cells. Nuclear factor kappa B (NF-kB) is a regulator for different biological responses, including cell proliferation and differentiation. In acute myeloid leukemia (AML), constitutive NF-kappaB has been detected in more than 50% of cases, enabling leukemic cells to resist apoptosis and stimulate uncontrolled proliferation. We evaluated NF-kB expression in bone marrow samples from 103 patients with AML using quantitative real time polymerase chain reaction (RT-PCR) and found that expression was increased in 80.5% (83 out 103) of these patients with AML in comparison to the control group. Furthermore, overexpressed transmembrane glycoprotein (CD44) on leukemic cells in comparison to normal cells is known to play an important role in leukemic cell engraftment and survival. We designed poly lactide co-glycolide (PLGA) nanoparticles conjugated with antiCD44 and encapsulating parthenolide (PTL), a nuclear factor kappa B (NF-kB) inhibitor, in order to improve the selectivity and targeting of leukemic cells and to spare normal cells. In vitro, in leukemic cell lines Kasumi-1, KG-1a, and THP-1, proliferation was decreased by 40% (** p < 0.01) with 5 microM PLGA-antiCD44-PTL nanoparticles in comparison to the same concentration of free PTL (~10%). The higher uptake of the nanoparticles by leukemic cells was confirmed with confocal microscopy. In conclusion, PLGA-antiCD44-PTL nanoparticles improved the bioavailability and selective targeting of leukemic cells, thus holding promise as a drug delivery system to improve the cure rate of AML. FAU - Darwish, Noureldien H E AU - Darwish NHE AUID- ORCID: 0000-0002-4124-9772 AD - Hematology Unit, Clinical Pathology Department, Mansoura Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt. nour_darwish83@yahoo.com. AD - The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA. nour_darwish83@yahoo.com. FAU - Sudha, Thangirala AU - Sudha T AD - The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA. Sudha.thangirala@acphs.edu. FAU - Godugu, Kavitha AU - Godugu K AD - The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA. Kavitha.godugu@acphs.edu. FAU - Bharali, Dhruba J AU - Bharali DJ AD - The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA. Dhruba.bharali@acphs.edu. FAU - Elbaz, Osama AU - Elbaz O AUID- ORCID: 0000-0002-2460-9422 AD - Hematology Unit, Clinical Pathology Department, Mansoura Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt. osamaelbaz@yahoo.com. FAU - El-Ghaffar, Hasan A Abd AU - El-Ghaffar HAA AD - Hematology Unit, Clinical Pathology Department, Mansoura Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt. haabdelghaffar@yahoo.com. FAU - Azmy, Emad AU - Azmy E AD - Clinical Hematology Unit, Mansoura University Oncology Center, Mansoura University, Mansoura 35516, Egypt. dremadazmy7@gmail.com. FAU - Anber, Nahla AU - Anber N AUID- ORCID: 0000-0001-5684-9298 AD - Fellow of Biochemistry Emergency Hospital, Mansoura University, Mansoura 35516, Egypt. nahla.anber@yahoo.com. FAU - Mousa, Shaker A AU - Mousa SA AUID- ORCID: 0000-0002-9294-015X AD - The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA. shaker.mousa@acphs.edu. LA - eng PT - Journal Article DEP - 20190603 PL - Switzerland TA - Molecules JT - Molecules (Basel, Switzerland) JID - 100964009 RN - 0 (Antigens, CD) RN - 0 (Biomarkers, Tumor) RN - 0 (NF-kappa B) RN - 0 (Sesquiterpenes) RN - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer) RN - 2RDB26I5ZB (parthenolide) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Antigens, CD/metabolism MH - Biomarkers, Tumor/metabolism MH - Cell Line, Tumor MH - Cell Proliferation/drug effects MH - Cell Survival MH - Dynamic Light Scattering MH - Female MH - Humans MH - Kaplan-Meier Estimate MH - Leukemia, Myeloid, Acute/*drug therapy/*metabolism/pathology MH - Male MH - Middle Aged MH - NF-kappa B/*metabolism MH - Nanoparticles/*chemistry MH - Particle Size MH - Polylactic Acid-Polyglycolic Acid Copolymer/chemistry MH - Sesquiterpenes/analysis/pharmacology/*therapeutic use MH - Young Adult PMC - PMC6600366 OTO - NOTNLM OT - AML OT - nanoparticles OT - nanoparticles with antiCD44 and encapsulating parthenolide OT - poly lactide co-glycolide OT - targeted therapy COIS- All authors declare they have no conflict of interest. EDAT- 2019/06/06 06:00 MHDA- 2020/01/07 06:00 PMCR- 2019/06/03 CRDT- 2019/06/06 06:00 PHST- 2019/05/03 00:00 [received] PHST- 2019/05/24 00:00 [revised] PHST- 2019/05/29 00:00 [accepted] PHST- 2019/06/06 06:00 [entrez] PHST- 2019/06/06 06:00 [pubmed] PHST- 2020/01/07 06:00 [medline] PHST- 2019/06/03 00:00 [pmc-release] AID - molecules24112103 [pii] AID - molecules-24-02103 [pii] AID - 10.3390/molecules24112103 [doi] PST - epublish SO - Molecules. 2019 Jun 3;24(11):2103. doi: 10.3390/molecules24112103.